PROJECT SUMMARY Understanding the mechanisms by which cells detect, integrate, and respond to distinct signals is of fundamental importance to biological systems. Cnidarians, such as jellyfish, hydroids, and sea anemones, use specialized stinging cells called nematocytes to facilitate both sensation and secretion involved with prey capture and defense. Mechanical and chemical signals synergistically act on nematocytes to elicit rapid discharge of a hollow, barbed tubule (nematocyst) to pierce and envenomate prey. Given the energetically expensive, single-use nature of discharge, the mechanisms regulating this event must be tightly regulated but are not understood. Thus, the nematocyte represents a unique system to probe how cells distinguish and process salient signals to regulate organellar physiology and elicit a robust response. Here, I will determine how environmental stimuli are filtered and integrated to activate nematocyte discharge, as well as the receptors and transduction mechanisms used to produce an appropriate behavioral response. I recently developed a patch-clamp electrophysiology preparation using isolated nematocytes from the starlet sea anemone (Nematostella vectensis), which allows for examination of the electrical properties of these cells, including those crticial for sensory transduction and amplification. My preliminary experiments demonstrate that nematocytes express a unique voltage-gated calcium conductance with biophysical properties that mediate nematocyte activation only in response to the most salient environmental signals. Proposed experiments will further examine the relationship between electrical signaling and discharge (Aim 1), the structural basis for the unique calcium channel properties (Aim 2), and the mechanisms by which nematocytes detect and integrate sensory signals (Aim 3). Proposed fellowship training leverages a diverse mentorship team to facilitate my multifaceted research approach utilizing physiological, genetic, and behavioral analyses to provide insight into mechanisms underlying signal transduction, filtering, and the coupling of sensory transduction to organellar physiology. Thus, this research represents a foundational study using a unique model organism to reveal molecular and cellular mechanisms broadly applicable to cell biology, neuroscience, and evolution.